Ultrasound energy driven intraventricular catheter to treat ischemia

ABSTRACT

A method and apparatus for improving blood flow to an ischemic region (e.g., myocardial ischemia) a patient is provided. An ultrasonic transducer is positioned proximate to the ischemic region. Ultrasonic energy is applied at a frequency at or above 1 MHz to create one or more thermal lesions in the ischemic region of the myocardium. The thermal lesions can have a gradient of sizes. The ultrasound transducer can have a curved shape so that ultrasound energy emitted by the transducer converges to a site within the myocardium, to create a thermal lesion without injuring the epicardium or endocardium.

BACKGROUND

1. Field of the Invention

The invention relates generally to treatment of heart disease. Moreparticularly, the invention is directed to an ultrasonic method andapparatus to treat ischemic tissue.

2. Description of the Background

Heart disease is a significant health problem and impairs the quality oflife for millions of people. A common form of heart disease is ischemicheart disease, a condition in which parts of the heart muscle, ormyocardium, do not receive an adequate supply of blood. Typically, thiscondition occurs when the arteries that carry blood to the myocardiumbecome clogged by plaque build-up on their inner walls. The cloggedarteries hinder blood flow, and the myocardium is deprived of oxygen andother nutrients. Ischemia results.

A number of methods are employed to improve blood flow to myocardiumdownstream of an arterial blockage. Many of these methods, such ascoronary bypass surgery and balloon angioplasty, involve circumventionor removal of the arterial obstruction to re-establish blood flow. Analternate set of methods, known as transmyocardial revascularization(TMR) or percutaneous transmyocardial revascularization (PMR), involvethe creation of small channels in the myocardium itself to reperfuse theischemic tissue.

Channels created by the TMR or PMR procedures were initially believed torelieve ischemia by allowing blood to flow directly from the ventricleinto the ischemic myocardium. More recent studies suggest that thechannels do not remain open. Instead, the TMR or PMR procedures maystimulate angiogenesis, the creation of new blood vessels, and it is thenew blood vessels that restore blood flow to the ischemic region.Angiogenesis is a natural response to cellular damage and results wheninjured cells alert the body to heal itself. It is believed that cellsdamaged by the TMR or PMR procedures produce and excrete specialchemicals, such as cytokines and growth factors, which signalsurrounding cells to initiate the formation of new blood vessels. Thenew blood vessels grow into the ischemic region, supplying the regionwith blood.

TMR and PMR methods used to create channels in the myocardium includemechanical coring, ultrasonic cutting, laser drilling, and using radiofrequency (RF) energy to burn through the heart tissue. The mechanical,ultrasonic, laser, or RF device is typically positioned at the end of acatheter. The catheter is inserted either through the patient'scardiovascular system to place the device into the inside of the heartor through a small cavity in the patient's chest to place the deviceonto the outside of the heart.

Mechanical coring methods create channels in the myocardium bydisplacing or removing the heart tissue. Cutting devices such as needlesor blades are employed.

Ultrasonic devices, such as those described in U.S. Pat. No. 5,827,203to Nita and U.S. Pat. No. 5,989,274 to Davison et al., are also used tomechanically scrape or cut channels into the heart tissue. With thesedevices, ultrasonic energy is applied at frequencies between 20 kHz and100 kHz to a tip at the end of a catheter. The ultrasonic energy causesthe tip to vibrate and pierce the surface of the heart to form achannel. A blade may be attached to the tip to facilitate cutting.

Lasers, such as CO₂ lasers, vaporize the heart tissue to burn channelsin the myocardium. Myocardial revascularization using lasers isdescribed, for example, in U.S. Pat. No. 6,074,384 to Brinkmann et al.

RF energy can also be used to burn holes in the myocardium, as describedin U.S. Pat. No. 6,030,380 to Auth et al., U.S. Pat. No. 5,944,716 toHektner, and U.S. Pat. No. 6,032,674 to Eggers et al.

A problem with the above procedures is that creating channels in themyocardium causes excessive trauma and damage to the heart tissue. Theepicardium, endocardium, or both are punctured to form the channels,leading to a risk of complications such as hemorrhaging and scarring.The possibility that an embolus will form and cause, for instance, astroke is another potential complication with the procedures.

As to problems with the particular methods described above, laser energyis known to kill healthy cells, which may worsen the patient'scondition. The laser procedure may also cause denervation, whichrelieves the chest pain associated with ischemia, but permanentlydamages the heart muscle. In addition, controlling the location anddepth of a channel formed by laser or RF energy is difficult, makingaccidental damage to healthy tissue more likely. RF energy is alsodiffuse, making it especially difficult to localize damage from the RFenergy device, and creating problems such as the coagulation ofsurrounding blood.

U.S. Pat. No. 5,827,203 also describes using low frequency ultrasonicenergy to massage the ischemic myocardium, without cutting or removingthe tissue, as is required when creating channels. However, althoughmassaging the tissue is less traumatic to the heart tissue than creatingchannels, massaging alone does not fully treat ischemia and does notcause the cellular damage necessary to stimulate angiogenesis.

SUMMARY

Embodiments of the present invention include methods and apparatuses fortreating ischemic myocardium. The invention minimizes injury to theheart tissue and risk to the patient while still causing the cellulardamage believed necessary for revascularization of ischemic tissue.

In one embodiment, an ultrasonic device is used to form localized,precisely placed thermal lesions in and near the ischemic tissue.Ultrasonic energy can be advantageously locally directed and isrelatively easy to control. Therefore, the thermal lesions formed byultrasonic energy can induce angiogenesis in myocardium without creatingchannels and without excessive damage and trauma to the tissue. Evenbeyond inducing angiogenesis, it is believed that the method will assistin increasing blood flow to the treated region and mitigates theprogression and symptoms of ischemia.

In one particular embodiment, a catheter having a distal end is insertedinto the patient. The catheter has at least one ultrasonic transducer onthe distal end. The ultrasonic transducer is positioned proximate to theischemic region. Ultrasonic energy is applied at a frequency at or above1 MHz to create a first thermal lesion in the ischemic region of themyocardium. For example, the ultrasonic energy can be applied atfrequencies between 4 MHz and 15 MHz to create the thermal lesion.

The method may further include repositioning the ultrasonic transducerand applying ultrasonic energy at a frequency at or above 1 MHz tocreate one or more second thermal lesions in the myocardium. The secondthermal lesion(s) may be created in the ischemic region adjacent thefirst thermal lesion or in myocardium adjacent the ischemic region. Thefirst and second lesions can be created so as to have a gradient ofsizes.

An embodiment of an ultrasonic catheter within the present invention canhave an array of ultrasonic transducers. Ultrasonic energy at afrequency greater than approximately 1 MHz can be applied from theultrasonic transducers in the array to create additional thermallesions. The ultrasonic transducers of the array may be independentlycoupled to a power source and independently controlled by a controller,allowing ultrasonic energy of varying power and duration to beindependently applied from each transducer in the array. The controllercan control the duty cycle of the power source, so that higher powerscan be applied to the tissue without overheating the transducer. Theindependently controlled transducers in the array can advantageously beused to create multiple thermal lesions that have a gradient of sizes.

The ultrasonic transducer can have a shape that causes the ultrasonicenergy emitted by the transducer to converge in a region locatedinternal to the myocardium and at a distance from the endocardium andepicardium. The transducer can have, for example, a bowl-like, partialcylinder, or hollow hyperboloid-like shape. Accordingly, the thermallesions produced by the converging ultrasonic energy will be locatedinternal to the myocardium and distal from the endocardium andepicardium. This allows ischemic region internal to the myocardium to betreated without injuring the endocardium or epicardium.

These and other embodiments and aspects of the present invention will bebetter understood in view of the attached drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a diagrammatic view of a human heart in partial cross sectionshowing a catheter with a distal end proximate to an ischemic region ofthe myocardium.

FIG. 2A illustrates a “side-fire” ultrasound transducer of a catheterthat is located adjacent to an ischemic region of the myocardium, and athermal lesion produced in the ischemic region by ultrasound energy fromthe transducer.

FIG. 2B is a plan view of a catheter with a transducer on the distalend. Electrical leads connect the transducer to a power supply andcontroller.

FIGS. 3A, 3B, and 3C illustrate multiple thermal lesions in the ischemicregion and myocardium adjacent the ischemic region with arrowsindicating the direction of concentration gradients of growth factorsand other angiogenesis stimulating substances. In FIG. 3A, the thermallesions are approximately equivalent in size, in FIGS. 3B and 3C, thethermal lesions decrease in size from the center of the ischemic region.

FIG. 4 illustrates a catheter having an array of ultrasound transducerspositioned over the ischemic region and the multiple lesions produced bythe ultrasound energy from transducers in the array.

FIG. 5 is a sectional representation of a portion of the array oftransducers illustrated in FIG. 4 and the electrical leads connectingthe transducers to the power source and controller.

FIG. 6 is a sectional representation of an internal ischemic region thatis located within the myocardium and a thermal lesion centered in theischemic region. The lesion does not contact the endocardium orepicardium.

FIG. 7 is a sectional representation of a concave ultrasound transducerelement located on the myocardium of FIG. 6, where ultrasound energydelivered from the concave transducer element is focused into theischemic region.

FIGS. 8A and 8B illustrate exemplary curves that the transducerillustrated in FIG. 7 may be shaped as to focus the ultrasound energy.

FIGS. 9A, 9B, and 9C illustrate exemplary ultrasound transducers shapedto focus ultrasound energy.

FIG. 10 is a sectional end-on view of a concave ultrasound transducermounted in a catheter.

FIG. 11 illustrates a catheter having multiple concave transducerelements and lesions produced in an internal ischemic region andadjacent myocardium by the ultrasound energy delivered by thetransducers.

DETAILED DESCRIPTION

FIG. 1 illustrates a heart 100 having an ischemic region 102 in themyocardium 104 of the left ventricle 106. A catheter 110 has beeninserted into the left ventricle 106. An ultrasound transducer 115 ismounted on distal portion 117 of catheter 110. Ultrasound transducer 115is positioned adjacent to the endocardial surface 107 and proximate toischemic region 102, where it is used to treat ischemic region 102, asdescribed below. In particular, transducer 115 is positioned on theendocardial surface 107 laterally adjacent ischemic region 102.

Although FIG. 1 illustrates ischemic region 102 and catheter 110 in theleft ventricle 106, which is particularly susceptible to ischemia, thebeneficial effect of the procedures and devices described herein can beused to treat any ischemic area of the heart or other body tissue.

FIG. 2A illustrates a portion of myocardium 104 with an ischemic region102. Ultrasound transducer 115 on catheter 110 is oriented towardischemic region 102. A thermal lesion 200 has been created in ischemicregion 102 by ultrasound energy that was emitted from ultrasoundtransducer 115 at a frequency at or above 1 MHz.

As defined herein, a “thermal lesion” is a localized injury to tissuecaused by application of ultrasonic energy at frequencies at or above 1MHz. In the various embodiments of the invention, such thermal lesionsare created to treat the ischemic tissue. Ultrasonic energy delivered totissue at frequencies at or above 1 MHz heats the tissue to cause damageto cells within the area of the lesion. It is believed that the cellsdamaged by the high-frequency ultrasonic energy produce angiogenesisstimulating substances such as cytokines and growth factors. Theangiogenesis stimulating substances promote the growth of new bloodvessels, which may grow toward, away from, and/or in the vicinity of theangiogenesis stimulating substances. Thus, the tissue in and around thethermal lesion is revascularized.

By contrast, the above-described ultrasonic references (i.e., Nita andDavison et al.) use ultrasound energy having a frequency of 20 kHz to100 kHz to shake an end effector against the tissue, thereby producinggross mechanical motion of the tissue. The gross mechanical motionmassages and shakes the tissue, but does not cause revascularization. Inthe embodiments of the present invention, the ultrasonic transducersends ultrasonic energy directly into the tissue at frequencies thatbegin at 1 MHz, e.g. 10 MHz, at least an order of magnitude higher thanthe above references, to obtain molecular motion and thus cause therequisite thermal cellular damage.

Such thermal lesions can be created using, for example, the ultrasounddevice described in U.S. Pat. No. 5,735,280 to Sherman and Castellano,which patent is incorporated herein by reference in its entirety. In thefollowing discussion, aspects of such a device, and modificationsthereto in accordance with the present invention are discussed indetail.

As illustrated in FIG. 2B, transducer 115 is connected to a power source530 and controller 531 via electrical leads 240 that traverse the lengthof catheter 110. Power source 530 provides energy to transducer 115through electrical leads 240. Controller 531 (typically containing amicroprocessor) controls the power supplied to transducer 115 from powersource 530. Ultrasound transducer 115 is typically a piezo-electriccrystal that can deliver ultrasonic energy at frequencies greater than 1MHz. In this embodiment, transducer 115 is a cylindrical, “side-fire”transducer. Ultrasonic energy is emitted radially from the sides of thetransducer.

To create a thermal lesion, ultrasonic energy can be delivered to thetissue from transducer 115 at, for the example of a cylindricaltransducer, a power of between 2 and 20 watts, typically 8-10 watts fora duration time in the range of 15 to 300 seconds, typically 120seconds. The ultrasonic energy is delivered at a frequency at or above 1MHz, e.g., between 1 MHz and 15 MHz, or more typically between 4 MHz and10 MHz.

In creating the thermal lesion(s) in accordance with the presentinvention, it is desirable to control the temperature of the ultrasoundtransducer 115. In particular, it is desirable to keep the transducerfrom getting so hot as to boil or carbonize blood or tissue thatdirectly contacts transducer 115. To avoid such a situation, thetemperature of the transducer is kept at or below 70° C. to 80° C., asmonitored by temperature sensors placed on the transducer crystal. Thetemperature sensors provide feedback to the controller, whichaccordingly adjusts the power supplied to transducer 115. The powersupplied to the transducer may be controlled by appropriate setting ofthe voltage level. Alternatively, the duty cycle of the power source canbe regulated in a manner that achieves high peak power while maintaininga relatively low effective power level, as described in U.S. Pat. No.5,971,980 to Sherman, which is incorporated herein by reference in itsentirety. Because the transducer cools more quickly than the tissue, theduty cycle can be used to keep the transducer below the desiredtemperature while maintaining the peak power level needed to create thethermal lesions.

Catheter 110 can be any surgical tool capable of advancing andpositioning ultrasound transducer 115. For example, catheter 110 can bea flexible guide catheter having a steerable tip, such as the catheterdescribed in U.S. Pat. No. 5,857,997. Catheter 110 may be fitted withadditional surgical equipment, such as a fiber optic scope for internalviewing, control circuitry for synchronizing delivery of ultrasoundenergy with the heartbeat cycle, or other devices for enhancing thesafety and effectiveness of the surgical method.

Methods for accessing the heart with a surgical tool such as catheter110 are well known. For example, catheter 110 can be inserted into thefemoral artery and maneuvered through the aorta and into the leftventricle or into one of the main coronary arteries such as the leftanterior descending or left circumflex. Alternatively, the heart can beexternally accessed by inserting catheter 110 through an opening in thepatient's chest, e.g., a sternotomy or mini-thoractomy, and positioningthe ultrasound transducer 115 adjacent the epicardial surface orpericardial sac. Fluoroscopic, ultrasound, or other imaging techniquescan be used to view catheter 110 and transducer 115 as they are guidedthrough the body and positioned proximate to ischemic region 102. Thelocation within the body of ischemic region 102 can be identified byknown techniques, such as angiography. Note also that creation ofthermal lesions in accordance with the embodiments of the invention maybe performed in conjunction with other procedures, for example coronaryartery bypass graft (CABG) surgery.

Exemplary Treatment Regimes

As mentioned above, we believe that, by creating thermal lesions inmyocardium using ultrasonic energy applied at a frequency at or above 1MHz without cutting or piercing the tissue, the tissue will besufficiently damaged to release angiogenesis stimulating substances. Thethermal lesions do not traumatize the tissue to the degree ofconventional TMR and PMR procedures. In the description below, varioustreatment regimes are discussed which provide thermal lesions in variouslocations and amounts, as may be appropriate to particular clinicalsituations.

A. Creating Multiple Thermal Lesions

Multiple thermal lesions, as illustrated by exemplary thermal lesions301, 302, and 303 of FIG. 3A, may be created throughout the ischemicregion. We believe that the damaged cells in the thermal lesion willrelease angiogenesis stimulating substances, such as growth factors andcytokines, and that new blood vessels will grow in the vicinity of thesubstances so released. In a larger ischemic region, multiple thermallesions throughout the ischemic region will cause angiogenesisstimulating substances to be released throughout the region, and thuspromote revascularization of the entire region. The number of thermallesions needed to treat an ischemic area depends on factors such as thesize of the ischemic area and degree of ischemia, as determined by thephysician, and the size of the thermal lesions produced. The size of thethermal lesion produced, in terms of the surface area of the ischemictissue covered by the thermal lesion, generally corresponds to the sizeof the transducer and the amount of contact the transducer has with thetissue. Typically, transducer 115 is 1 to 10 mm long and 1 to 10 mm inwidth (e.g., the diameter of a cylindrical transducer), creating thermallesions that cover a surface area 1 to 10 mm in length and 1 to 10 mm inwidth. Typically, at least one thermal lesion is created for each squarecentimeter (cm²) of ischemic region.

FIG. 3A also illustrates thermal lesions 304 and 305, which may becreated in region 103 adjacent the ischemic region, where the hearttissue is healthier. New blood vessels may form more readily in thehealthier tissue and may grow from the healthier tissue in region 103toward the angiogenesis stimulating substances produced by the damagedcells in thermal lesions 301, 302, and 303, as illustrated by the arrows310 and 311.

In another embodiment, illustrated by the example of FIG. 3B, the sizeof the thermal lesions is varied to produce a gradient of sizes of thethermal lesions. Larger thermal lesions, such as thermal lesion 320, arecreated towards the center of the ischemic tissue. The larger thermallesions 320 typically release larger amounts of angiogenesis stimulatingsubstances than do the smaller thermal lesions 322 at the edges of theischemic region. Thus, the size gradient of thermal lesions creates aconcentration gradient of the released angiogenesis stimulatingsubstances, illustrated by arrows 325, 326. It is believed that more newblood vessels may grow in the vicinity of the higher concentrations ofthe angiogenesis stimulating substances or that the higher concentrationmay stimulate the new blood vessels to grow over a larger distance. Thegradient of sizes of the thermal lesions therefore may promote growth ofnew blood vessels in the center of ischemic region 102.

For a given size of transducer 115, the size of a thermal lesion can bevaried by varying the power output of the ultrasound transducer. Thepower output can be varied either by varying the voltage applied totransducer 115, the duty cycle (as described above), or the frequency ofthe ultrasound energy. In general, for transducer geometries such ascylindrical or flat, in which the ultrasound energy that radiates fromthe transducer does not converge (see below), more power creates adeeper lesion. The distance the transducer is from the myocardial tissuewill also determine how deep into the tissue the ultrasonic energypenetrates and, hence, the size of the thermal lesion.

FIG. 3C illustrates an alternative embodiment that combines the methodsillustrated in FIGS. 3A and 3B. Thermal lesions 340, 341, 342, 343, and344 of varied size are created across ischemic region 102 and are alsocreated in the area 103 adjacent the ischemic region.

To make the multiple thermal lesions illustrated in FIGS. 3A-3C with acatheter 110 having a single transducer element 115, as illustrated inFIG. 2B, transducer 115 is repositioned each time a new thermal lesionis to be created. However, if multiple thermal lesions are to becreated, single transducer 115 must be repositioned several times, whichcan make the procedure lengthy and may expose the patient to additionalrisk of complications.

An alternative apparatus that avoids or reduces the need to repositiontransducer 115 several times is illustrated in FIG. 4. An array 415 oftransducers 115 is provided at the distal end of catheter 110. While tentransducers 115 are shown in array 415 of FIG. 4, the number oftransducers may be more or less, and catheter 110 typically contains anarray of between 5 and 15 ultrasound transducers 115 depending on theapplication. The spacing 416 between each transducer 115 can also varywith the application. For example, in one treatment regime, a thermallesion is created for every one square centimeter of surface area ofischemic region 102 on the endocardium or epicardium. To treat anischemic region 102 that has 25 cm² surface area and that isapproximately square (5 cm×5 cm), a catheter 110 should have an array415 of at least 5 transducers with, for instance, one transducer per cmin the array (e.g., transducers of 4 mm in length with a spacing 416 of6 mm between them). To cover the 25 cm² ischemic area, such an array canbe positioned five times to create five lines of five thermal lesionsfor a total of 25 thermal lesions. With respect to the spacing 416,small, tightly spaced ultrasound transducers can be used to make small,tightly spaced thermal lesions, but may make distal end 117 of catheter110 less flexible.

The transducer array 415 only needs to be positioned so that a portionof the transducers 115 overlies ischemic region 102. Radiopaque or othermarkers on the catheter can be used to identify which of the transducers115 are located over the ischemic region 102 and adjacent region 103.The identified transducers can be selectively activated by thecontroller to produce thermal lesions in region 102 and, if desired,region 103. The controller can also individually control the poweroutput (by controlling the voltage, duty cycle, and/or frequency) ofeach transducer, to produce thermal lesions of varying sizes. Typicallycatheter 110 having an array 415 of transducers 115 will not need to berepositioned, or will only need to be repositioned a relatively smallnumber of times, to create the desired pattern of thermal lesions acrossthe entire ischemic region 102. The size of ischemic region 102typically will be a factor in determining whether any repositioning ofarray 415 will be necessary.

Typically, each transducer 115 of multi-transducer catheter 110 isindividually coupled to the power source. As illustrated in theembodiment of FIG. 5, each of the multiple transducers 115 has anelectrical lead 501 connected to the outer surface 510 of the transducerand an electrical lead 502 connected to the inner surface 520 of thetransducer. Electrical leads 501, 502 can be narrow (44-48 gauge)coaxial cable or twisted pair balanced feed line. The coaxial cablecontains an inner wire for carrying the electrical signal, and a groundwire surrounding the inner wire to shield the inner wire from electricalnoise. Coaxial cables or twisted pair balanced feed lines are typicallyused for electrical leads 501, 502 instead of bare wire to minimizeimpedence loss over the length of the wire due to standing wavereflections. Electrical leads 501, 502 run through an inner lumen 511 ofcatheter 110 to the power source, and are flexible, so as not to hinderplasticity of catheter 110. Inner lumens 511 will also containcomponents (not shown) for steering and guiding catheter 110 through thebody.

Electrical leads 501, 502 deliver energy to the transducers 115 from apower source 530. Controller 531 controls power source 530. Thecontroller 531 (typically containing a microprocessor) can be programmedto selectively turn on and individually control each transducer 115.Transducers 115 can be activated simultaneously or sequentially, andpower can be controlled to each using the amplitude of the voltage, dutycycle, or frequency as described above.

B. Creating Thermal Lesions Located Internal to the Myocardium

A method of treatment within the present invention uses ultrasonicenergy having a frequency at or above 1 MHz to create thermal lesion(s)that are internal to the myocardium and advantageously do not damage theendocardium or epicardium. FIG. 6 illustrates an embodiment of thismethod, where a thermal lesion 600 has been created at a depth D withinthe myocardium 104. Thermal lesion 600 does not overlap the endocardium107 or the epicardium 108. Likewise, thermal lesion 600 does not overlaphealthy myocardium 612 between the endocardium 107 or epicardium 108 andthe ischemic region 102.

FIG. 7 illustrates a curved ultrasonic transducer 715 for creatingthermal lesion 600 of FIG. 6. Transducer 715 is similar to transducer115, except that transducer 715 is shaped so that ultrasonic energy 710radiates from the concave surface 720 and converges at a site 712 beyondthe transducer. Transducer 715 can be positioned over ischemic region102 and set on the endocardial 107 (or epicardial 108) surface ofmyocardium 104 with the concave surface 720 facing the myocardium.Ultrasound energy emitted from transducer 715 will be focused in theischemic region to form thermal lesion 600.

Transducer 715 can have, for instance, a spherical curve, as illustratedin FIG. 8A by exemplary curve 800, a parabolic curve, as illustrated byexemplary curve 801 of FIG. 8B, or any other shape that focuses theultrasound energy. For transducer 715 having a given shape, such ascurve 800, ultrasonic energy 710 will radiate from the concave side 720of the curve and converge at a focal site F. The depth D that thermallesion 600 is created within myocardium 104 is determined by the lengthL_(D) that focal site F extends beyond the ends E of the curve. LengthL_(D) is determined by the degree of curvature and arc length of thecurve. Healthy myocardium has a thickness, T, (shown in FIG. 7) ofapproximately 1-2 mm, but the myocardium of diseased hearts can bethicker, for instance up to approximately 7 mm. Therefore, the depth Dof thermal lesion 600 can be set to between, for example, 1 and 7 mm.

Curved transducer 715 can have a variety of shapes, including, but notlimited to, the exemplary shapes illustrated in FIGS. 9A, 9B, and 9C.FIG. 9A illustrates transducer 715 in an exemplary bowl-like shapeformed by the surface of rotation of a curve, such as curve 800 or 801,about the x-axis in FIGS. 8A and 8B, respectively. Ultrasonic energy 710radiating from a transducer 715 of FIG. 9A converges in a central site,for example, site 925.

FIG. 9B illustrates transducer 715 having an exemplary shape that is apartial cylinder formed by the surface of translation of a curve, suchas curve 800 or 801, along the z-axis of FIGS. 8A and 8B, respectively.Ultrasonic energy 710 emanating from transducer 715 of FIG. 9B convergesalong line 926, having a length L approximately equal to the lengthL_(t) of the transducer.

FIG. 9C illustrates transducer 715 having an exemplary hollow tubularshape with flared ends, such as a hyperboloid-like shape, formed by thesurface of rotation of the curve, such as curve 800 or 801, about they-axis in FIGS. 8A and 8B, respectively. Ultrasonic energy 710 radiatingfrom transducer 715 of FIG. 9C converges along a circle 927 surroundingthe transducer. Therefore, ultrasound energy emitted from ahyperboloid-like shaped transducer 715 will form a thermal lesion in theform of an arc through the tissue, damaging the endocardial (orepicardial) surface at the point where the circle 927 intersects theendocardial (or epicardial) surface. However, a hyperboloid-like shapedtransducer advantageously does not have to be oriented in a particulardirection to irradiate ultrasound energy into the tissue.

Shaped transducer 715 can be formed by cutting, typically with anultrasonic or mechanical machining process, sintering a powder of, ormolding the ceramic material into the desired shape. The shaped ceramicis then polarized in a known process, for example exposing the ceramicto a high electric field, so that it will radiate ultrasound energy.Transducer 715 can be formed from, for example, LTZ2 (Staveley Sensors,Inc., East Hartford, Conn.), PZT, or other lead-ceramic materials, suchas PbTiO₃ (lead titanate) or PbZrO₃ (lead zirconate).

The resonant frequency of the transducer is inversely proportional tothe thickness of the ceramic material. Typically the ceramic material isbetween 0.006 inch (0.15 mm) to 0.015 inch (0.38 mm) thick, depending onthe desired resonant frequency. The longest dimension of transducer 715is typically between 1 and 10 mm.

FIG. 10 illustrates a sectional view of concave transducer 715 mountedin catheter 110. The front 720 and back 721 surfaces of the transducer715 are typically coated with conductive material plating (not shown),such as gold, platinum or palladium, or other similar conductivematerials. A thin layer of a bio-compatible coating 727, such as Epo-Tek353 ND (Epo-Tek, Inc., Billerica, Mass.) or parylene is typicallyapplied to concave surface 720. Coating 727 protects and strengthens thetransducer, electrically isolates the conductive surfaces, and can beused to match impedance between the crystal and the tissue.

The transducer 715 is mounted to the catheter 110 through an o-ring 790,or other mechanical means that seals transducer 715 to catheter 110.Solder joints are used to mechanically attach and electrically connectthe electrical leads 501, 502 to the transducer 715. In addition tosolder joints, a conductive epoxy, cold solders, ultrasonic welds andother similar attachment techniques can be used. Electrical leads 501,502 are generally connected at the edge of transducer 715 because soldermay dampen the vibrations of the transducer.

There is a gap 780 between transducer 715 and catheter 110. Gap 780 maycontain any suitable low-density material, including gaseous substancessuch as ambient air, oxygen, nitrogen, helium, an open-cell polymericfoam, a closed cell polymeric foam, and other similar polymericmaterials and mixtures thereof. Ultrasonic energy does not travelthrough low-density material but instead is reflected by the low-densitymaterials. Therefore, the ultrasonic energy that radiates inward fromtransducer 715, off back surface 721, is reflected rather than beingabsorbed by the catheter. Gap 780 can be extremely thin, for example,{fraction (1/1000)} of an inch (0.025 mm), to leave room within catheter110 for electrical leads 501,502 and additional steering and guidingcomponents (not shown). Catheter 110 is typically between 5 and 8 frenchin diameter.

Because the ultrasonic energy emitted from transducer 715 is focused,less power, for example, 2-3 Watts, is typically needed to create thethermal lesion 600 than to create a thermal lesion from an unfocusedtransducer. The duration of application of the ultrasonic energy will besimilar to those listed above.

FIG. 11 illustrates a catheter 110 having an array 415 of curvedtransducers 715 at a distal end. Curved transducers 715, illustratedhere as having the exemplary hyperboloid-like shape illustrated in FIG.9C, focuses ultrasonic energy as described above. The transducers 715 inarray 415 are connected to a power source and controller as illustratedin FIG. 5 and operate in the same manner as described above with respectto FIG. 5.

In FIG. 11, multiple thermal lesions 601, 602, 603, 604, 605 have beencreated at a depth D within myocardium 104 by transducers 715 in array415. The thermal lesions have a gradient of sizes, as described abovewith respect to FIG. 3B, and lesions 601 and 605 have been createdwithin the healthier tissue of region 103, as describe above inreference to FIG. 3A.

While particular embodiments of the present invention have been shownand described, it will be clear to those of ordinary skill in the artthat changes and modifications can be made without departing from thisinvention in its broader aspects and, therefore, the appended claims areto encompass all such changes and modifications as falling within thescope of this invention.

What is claimed is:
 1. A method of treating an ischemic region of a patient, comprising: positioning an ultrasonic transducer proximate to said ischemic region; and applying an ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create a thermal lesion in about the center of said ischemic region, wherein said ultrasonic energy is applied without piercing or cutting said ischemic region.
 2. The method of claim 1, wherein said ultrasonic energy is applied at a frequency between 4 megahertz and 15 megahertz.
 3. The method of claim 1, further comprising: repositioning said ultrasonic transducer; and applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create one or more second thermal lesions in the myocardium; wherein at least one second thermal lesion is created in said ischemic region adjacent said thermal lesion, or is created in myocardium adjacent said ischemic region; and wherein said thermal lesion is larger than said at least one second thermal lesion.
 4. The method of claim 1, further comprising controlling the temperature of said transducer to be maintained below approximately 80° C. during the procedure.
 5. The method of claim 1, wherein said ultrasonic transducer is inserted inside a heart of the patient.
 6. An apparatus for creating multiple thermal lesions in biological tissue, comprising: a catheter; an array of ultrasonic transducers mounted on a distal portion of said catheter; a power source that provides energy through said catheter to said ultrasonic transducers; and a controller to control the energy provided to said ultrasonic transducers from said power source, said controller configured to control the duty cycle of said power source so that the temperature of said ultrasonic transducers remains at or below 80° C. during a procedure.
 7. The apparatus of claim 6, wherein said ultrasonic transducers of said array are each independently coupled to said power source and independently controlled by said controller.
 8. The apparatus of claim 6, further comprising a temperature sensor mounted on a distal end of said catheter, said temperature sensor in communication with said controller to provide feedback to said controller.
 9. An apparatus for creating thermal lesions within biological tissue, comprising: a catheter; an ultrasonic transducer mounted on a distal end of said catheter, said ultrasonic transducer having a curved surface configured so that ultrasonic energy is radiated from said curved surface to converge on a region beyond said transducer; a power source that provides energy through said catheter to said ultrasonic transducer; and a controller for controlling the energy provided to said ultrasonic transducer from said power source.
 10. The apparatus of claim 9, wherein said transducer comprises a partial cylinder, a bowl-like shape, a tubular shape, or a hyperboloid-like configuration.
 11. The apparatus of claim 9, further comprising one or more additional ultrasonic transducers mounted on said distal end of said catheter.
 12. The apparatus of claim 11, wherein said additional transducers have a curved surface configured so that ultrasonic energy is radiated from said curved surface to converge in a region beyond said transducer.
 13. The apparatus of claim 11, wherein one or more of said ultrasonic transducers are independently coupled to said power source and independently controlled by said controller.
 14. The apparatus of claim 9, wherein the curved surface comprises a conductive material plating.
 15. The apparatus of claim 14, wherein said conductive material plating comprises gold, platinum or palladium.
 16. A method of treating an ischemic region of a patient, comprising: positioning an ultrasonic transducer proximate to said ischemic region; applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create a first thermal lesion in said ischemic region; repositioning said ultrasonic transducer; and applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create one or more second thermal lesions in the myocardium; wherein at least one second thermal lesion is created in said ischemic region adjacent said first thermal lesion.
 17. The method of claim 16, wherein said thermal lesion and said one or more second thermal lesions are created so as to have different sizes.
 18. The method of claim 16, wherein said ultrasonic energy is applied at a frequency between 4 megahertz and 15 megahertz.
 19. The method of claim 16, further comprising controlling the temperature of said transducer to be maintained below approximately 80° C. during the procedure.
 20. The method of claim 16, wherein said ultrasonic transducer is inserted inside a heart of the patient.
 21. The method of claim 16, wherein said first thermal lesion is larger than said at least one second thermal lesion.
 22. The method of claim 16, wherein said first thermal lesion is smaller than said at least one second thermal lesion.
 23. A method of treating an ischemic region of a patient, comprising: positioning an ultrasonic transducer proximate to said ischemic region; applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create a first thermal lesion in said ischemic region; repositioning said ultrasonic transducer; and applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create one or more second thermal lesions in the myocardium; wherein at least one second thermal lesion is created in myocardium adjacent said ischemic region.
 24. The method of claim 23, wherein at least one second thermal lesion is created in said ischemic region of the myocardium adjacent said first thermal lesion.
 25. The method of claim 23, wherein said first thermal lesion is larger than said at least one second thermal lesion.
 26. The method of claim 23, wherein said first thermal lesion is smaller than said at least one second thermal lesion.
 27. The method of claim 23, wherein said ultrasonic energy is applied at a frequency between 4 megahertz and 15 megahertz.
 28. The method of claim 23, further comprising controlling the temperature of said transducer to be maintained below approximately 80° C. during the procedure.
 29. The method of claim 23, wherein said ultrasonic transducer is inserted inside a heart of the patient.
 30. The method of claim 23, wherein said first thermal lesion and said one or more second thermal lesions are created so as to have different of sizes.
 31. A method of treating an ischemic region of a patient, comprising: positioning an ultrasonic transducer proximate to said ischemic region, said ultrasonic transducer being connected to a power source having a controllable duty cycle; applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create a thermal lesion in said ischemic region, wherein said ultrasonic energy is applied without piercing or cutting said ischemic region; and controlling said duty cycle so that the temperature of said ultrasonic transducer remains at or below 80° C. during the procedure.
 32. The method of claim 31, wherein said ultrasonic energy is applied at a frequency between 4 megahertz and 15 megahertz.
 33. The method of claim 31, wherein said ultrasonic transducer is inserted inside a heart of the patient.
 34. A method of treating an ischemic region of a patient, comprising: positioning an ultrasonic transducer proximate to said ischemic region, wherein said ultrasonic transducer is one of an array of ultrasonic transducers; applying an ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create a thermal lesion in about the center of said ischemic region; and applying ultrasonic energy at a frequency at or above one megahertz from one or more ultrasonic transducers in said array to create one or more second thermal lesions in the myocardium.
 35. A method of treating an ischemic region of a patient, comprising: positioning an ultrasonic transducer proximate to said ischemic region; and applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create a thermal lesion in said ischemic region; wherein said ultrasonic energy is applied so that said thermal lesion is located internal to the myocardium and distal from an endocardium and an epicardium of the myocardium.
 36. The method of claim 35, further comprising applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create one or more second thermal lesions located internal to the myocardium and distal from said endocardium and epicardium.
 37. The method of claim 35, wherein said ultrasonic energy is applied at a frequency between 4 megahertz and 15 megahertz.
 38. The method of claim 35, further comprising controlling the temperature of said transducer to be maintained below approximately 80° C. during the procedure.
 39. The method of claim 35, wherein said ultrasonic transducer is inserted inside a heart of the patient.
 40. A method of treating an ischemic region of a patient, comprising: positioning an ultrasonic transducer proximate to said ischemic region; and applying ultrasonic energy at a frequency at or above one megahertz from said ultrasonic transducer to create one or more thermal lesions for about each square centimeter of said ischemic region, wherein said ultrasonic energy is applied without piercing or cutting said ischemic region.
 41. A method of treating an ischemic region of a patient, comprising: positioning an ultrasonic transducer on or near said ischemic region; applying an ultrasonic energy to a region adjacent said ischemic region to create a first thermal injury in said adjacent region; and applying an ultrasonic energy to said ischemic region to create at least one second thermal injury in said ischemic region.
 42. The method of claim 41, wherein said at least one second thermal injury is of different size than said first thermal injury.
 43. The method of claim 41, further comprising: repeating said application of an ultrasonic energy to create a plurality of thermal injuries.
 44. The method of claim 43, wherein said plurality of thermal injuries are created so as to form a gradient in size of thermal injuries. 